Selection of Therapeutic Strategies after Preoperative Neoadjuvant Chemoradiotherapy for Rectal Cancer

Rectal cancer is one of the most common malignant tumors in China, which is mainly middle and low rectal cancer. Due to the particularity of the physiological and anatomical location of the rectum and the neglect of the relevant clinical symptoms, patients with rectal cancer in real life often have the local progression stage. A large number of studies have shown that neoadjuvant chemoradiotherapy should be performed in such patients, to achieve tumor downstaging before rectal cancer surgery. In this study, different treatment measures for rectal cancer patients after neoadjuvant chemoradiotherapy are presented

Exploration of Treatment in Patients with T3 Rectal Cancer with EMVI

To explore the clinical efficacy of neoadjuvant chemoradiotherapy, combined with surgery and direct surgery in patients with stage T3 rectal cancer combined with EMVI. Method: The clinical data of patients with extragastrointestinal middle and low rectal cancer in the First Affiliated Hospital of Chongqing Medical University from January 2015 to May 2019 were retrospective reviewed, including 59 patients in the neoadjuvant treatment group (neoadjuvant chemoradiotherapy + surgical treatment) and 71 patients in the direct surgery group. Both groups underwent total rectal total membrane resection. Data and Methods:The concurrent chemotherapy regimens were all included in the XELOX regimen. The RT was performed by IMRT with D T 45 to 50.4 G y, from 1.8 to 2.0 G y each, for 25 to 28 sessions. Perioperative conditions, postoperative pathology and follow-up of the two groups were observed. Results: There was no significant difference in postoperative conditions (gastrointestinal function recovery time, postoperative drainage drainage, postoperative time of drainage removal) between the neoadjuvant treatment group and the direct surgery group (P> 0. 05); The length of postoperative hospital stay was significantly different (P <0.05); No significant operation time occurred between the neoadjuvant treatment group (264 min vs. 239 min) and the surgical group, (P> 0. 05)；The amount of intraoperative bleeding (85.7ml vs.110.0 ml), the number of lymph node dissection (11 vs. 13), the lymph node positive rate (27.12% vs.43.6%) betweenthe neoadjuvant treatment group and the direct surgery group had statistical significant (P＜0. 05); The 3-yearrecurrence-free survival (93.2 %) rate was higher in the neoadjuvant treatment group than in the direct surgery group (74.6 %), which was significant (P <0.05); The 3-year survival rate (98.30,% vs. 85.9 %) was significantly significant (P <0.05); There was no significant difference in the anal preservation rate (71.19% vs. 80.28%) (P> 0. 05). Conclusion: The neoadjuvant chemoradiotherapy improves the recurrence-free survival rate of locally advanced rectal cancer, and has no obvious effect on the postoperative complications rate, anal preservation rate and gastrointestinal function recovery

Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic

<p>Abstract</p> <p>Background</p> <p>To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic.</p> <p>Methods</p> <p>A survey conducted in 21 intensive care units in 17 provinces in China.</p> <p>Results</p> <p>Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001).</p> <p>Conclusion</p> <p>Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.</p

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Hematopoietic stem cell exhaustion impacted by p18INK4C and p21Cip1/Waf1 in opposite manners

Transplantation-associated stress can compromise the hematopoietic potential of hematopoietic stem cells (HSCs). As a consequence, HSCs may undergo “exhaustion” in serial transplant recipients, for which the cellular and molecular bases are not well understood. Hematopoietic exhaustion appears to be accelerated in the absence of p21Cip1/Waf1 (p21), a cyclin-dependent kinase inhibitor (CKI) in irradiated hosts. Our recent study demonstrated that unlike loss of p21, deletion of p18INK4C (p18), a distinct CKI, results in improved long-term engraftment, largely because of increased self-renewing divisions of HSCs in vivo. We show here that HSCs deficient in p18 sustained their competitiveness to wild-type HSCs from unmanipulated young mice, and retained multilineage differentiation potential after multiple rounds of serial bone marrow transfer over a period of more than 3 years. Further, p18 absence significantly decelerated hematopoietic exhaustion caused by p21 deficiency. Such an effect was shown to occur at the stem cell level, likely by a counteracting mechanism against the cellular senescence outcome. Our current study provides new insights into the distinct impacts of these cell-cycle regulators on HSC exhaustion and possibly HSC aging as well under proliferative stress, thereby offering potential pharmacologic targets for sustaining the durability of stressed HSCs in transplantation or elderly patients

Myeloid transformation of plasma cell myeloma: molecular evidence of clonal evolution revealed by next generation sequencing

Abstract Background Plasma cell myeloma (PCM) is a neoplasm of terminally differentiated B lymphocytes with molecular heterogeneity. Although therapy-related myeloid neoplasms are common in plasma cell myeloma patients after chemotherapy, transdifferentiation of plasma cell myeloma into myeloid neoplasms has not been reported in literature. Here we report a very rare case of myeloid neoplasm transformed from plasma cell myeloma. Case presentation A 60-year-old man with a history of plasma cell myeloma with IGH-MAF gene rearrangement and RAS/RAF mutations developed multiple soft tissue lesions one year following melphalan-based chemotherapy and autologous stem cell transplant. Morphological and immunohistochemical characterization of the extramedullary disease demonstrated that the tumor cells were derived from the monocyte-macrophage lineage. Next generation sequencing (NGS) studies detected similar clonal aberrations in the diagnostic plasma cell population and post-therapy neoplastic cells, including IGH-MAF rearrangement, multiple genetic mutations in RAS signaling pathway proteins, and loss of tumor suppressor genes. Molecular genetic analysis also revealed unique genomic alterations in the transformed tumor cells, including gain of NF1 and loss of TRAF3. Conclusion To our knowledge, this is the first case of myeloid sarcoma transdifferentiated from plasma cell neoplasm. Our findings in this unique case suggest clonal evolution of plasma cell myeloma to myeloma neoplasm and the potential roles of abnormal RAS/RAF signaling pathway in lineage switch or transdifferentiation

Identification of a novel monocytic phenotype in Classic Hodgkin Lymphoma tumor microenvironment.

Classic Hodgkin lymphoma (CHL) characteristically shows few malignant cells in a microenvironment comprised of mixed inflammatory cells. Although CHL is associated with a high cure rate, recent studies have associated poor prognosis with absolute monocyte count in peripheral blood and increased monocyte/macrophages in involved lymph nodes. Thus, the role of monocytic infiltration and macrophage differentiation in the tumor microenvironment of CHL may be more relevant than absolute macrophage numbers to defining prognosis in CHL patients and potentially have therapeutic implications. Most studies identify tumor-associated macrophages (TAMs) using markers (e.g., CD68) expressed by macrophages and other mononuclear phagocytes, such as monocytes. In contrast, Class A Scavenger Receptor (SR-A/CD204) is expressed by tissue macrophages but not monocytic precursors. In this study, we examined SR-A expression in CHL (n = 43), and compared its expression with that of other macrophage markers. We confirmed a high prevalence of mononuclear cells that stained with CD68, CD163, and CD14 in CHL lymph nodes. However, SR-A protein expression determined by immunohistochemistry was limited to macrophages localized in sclerotic bands characteristic of nodular sclerosis CHL. In contrast, SR-A protein was readily detectable in lymph nodes with metastatic tumor, extra-nodal CHL, T cell/histiocyte-rich large B cell lymphoma, and resident macrophages in non-malignant tissues, including spleen, lymph node, liver and lung. The results of SR-A protein expression paralleled the expression of SR-A mRNA determined by quantitative RT-PCR. These data provide evidence that tumor-infiltrating monocyte/macrophages in CHL have a unique phenotype that likely depends on the microenvironment of nodal CHL

A rare case of visceral leishmaniasis in an immunocompetent traveler returning to the United States from Europe.

A young, healthy traveler returning to the United States presented with fever, night sweats, splenomegaly, and pancytopenia. Bone marrow biopsy revealed leishmaniasis (Leishmania infantum), likely acquired in southern France. Although many cases of endemic visceral leishmaniasis (VL) have been reported in Europe, this is a rare case of imported VL in a healthy traveler returning from Europe to the US. Despite successful initial treatment with liposomal amphotericin B (LamB), relapse occurred. Treatments for VL in immunocompetent individuals are highly effective, but relapse can occur. There is more extensive experience in endemic areas with treating relapse that may be lacking in North America. This case alerts physicians in the US that immunocompetent adults can acquire VL during brief visits to endemic areas in Europe. It is important that travelers be counseled on preventive measures. Patients should be monitored after treatment for relapse

Preactivation of NKT cells with α-GalCer protects against hepatic ischemia-reperfusion injury in mouse by a mechanism involving IL-13 and adenosine A2A receptor

Hepatic preconditioning has emerged as a promising strategy of activating natural pathways to augment tolerance to liver ischemia-reperfusion (IR) injury. Liver-resident natural killer T (NKT) cells play an important role in modulating the local immune and inflammatory responses. This work was aimed to investigate whether preactivation of NKT cells could provide a beneficial “preconditioning” effect to ameliorate the subsequent hepatic IR injury. To selectively activate NKT cells, C57BL/6 mice were treated intraperitoneally with the glycolipid antigen α-galactosylceramide (α-GalCer) 1 h prior to hepatic ischemia. Significantly reduced liver IR injury was observed in mice pretreated with α- GalCer, and this protective effect was specifically abrogated by a CD1d blocking antibody. Serum TNF-α, IFN-γ, and IL-13 levels were markedly increased shortly after α-GalCer injection. Pretreatment with a neutralizing antibody against TNF-α or IFN-γ did not influence the protective effect of α-GalCer preconditioning, whereas preadministration of an IL-13 neutralizing antibody completely abolished the effect. Treatment with α-GalCer also led to an increased expression of adenosine A2A receptor (A2AR) in the liver, and blockade of A2AR by SH58261 diminished α-GalCer pretreatment-mediated attenuation of liver IR injury. In contrast, administration of the selective A2AR agonist CGS21680 reversed the counteracting effect of the IL-13 neutralizing antibody on α-GalCer preconditioning. Additionally, α-GalCer pretreatment was associated with a decreased neutrophil accumulation in the ischemic liver. These findings provide the first evidence that hepatic preconditioning by preactivation of NKT cells with α-GalCer protects the liver from IR injury via an IL-13 and adenosine A2AR-dependent mechanism